Peptides are generally administered parenterally, e.g., by subcutaneous injection, since they are often degraded in the gastrointestinal tract. Many peptide treatments (e.g., insulin, LHRH, and somatostatin) require either the continuous or repeated administration of the peptide in the patient over an extended period of time. However, such continual injections cause both inconvenience and discomfort to the patient. Sustained-release formulations have been developed to deliver peptides over prolonged periods of time without the need for repeated injections. Solid polymeric microcapsules and matrixes, for example, utilizing biodegradable polylactic polymers, have been developed. See e.g., Hutchinson, U.S. Pat. No. 4,767,628 and Kent, et al., U.S. Pat. No. 4,675,189. Hydrogels have also been used as sustained-release formulations for peptides. These hydrogels comprise polymers such as poly-N-isopropyl acrylamide (NIPA), cellulose ether, hyaluronic acid, lecithin, and agarose to control the delivery. See, e.g., PCT Applications WO 94/08623.
Some peptides have been reported to form soluble aggregates or insoluble particulates once mixed into a solution. See, Eckhardt, et al., Pharm. Res., 8:1360 (1991). Others have studied the possibility of utilizing these peptide aggregates as sustained-release formulations. See European Patent Application 0510913 A2 (1992); and Wan, et al., Pharmaceutical Research, Vol. 11, 10 Suppl., abstracts P. S291 and P. S243 (1994). However, these aggregate sustained-release compositions require that the peptide be dissolved in saline or biologically compatible buffers, and then incubated until a liquid crystalline gel structure is formed.
Elsewhere it has been reported that certain soluble peptide salts can be formulated as sustained-release gel formulations without the addition of a biodegradable polymer or other carrier matrix to control the peptide's release profile. See Cherif-Cheikh, U.S. Pat. No. 5,595,760.